Professor in Residence
M_Neurology
+1 415 502-7237
The goal of our research is to investigate mechanisms of longevity, resilience and neurodegenerative disease. Broadly we investigate how aging pathways can confer resilience to a brain and counter neurodegenerative diseases like Alzheimer’s. Using genetic mouse models, cell culture methods, and study of human populations using cutting-edge techniques, we study whether longevity-derived mechanisms can pave a path toward development of urgently needed therapies in aging and disease.
To this end, we are unraveling mechanisms that underlie female longevity, studying sex chromosomal contributions to neurodegenerative disease, and investigating the longevity hormone klotho in the normal and diseased brain.
Publications
More fit KL-VS heterozygotes have more favorable AD-relevant biomarker profiles.
Alzheimer's & dementia (New York, N. Y.)
Strategies for studying sex differences in brain aging.
Trends in genetics : TIG
Older more fit KL-VS heterozygotes have more favorable AD-relevant biomarker profiles.
medRxiv : the preprint server for health sciences
KLOTHO KL-VS genotype modifies the relationship between cardiorespiratory fitness and CSF biomarkers of neurodegeneration, synaptic dysfunction, and inflammation.
Alzheimer's & Dementia
Tlr7 drives sex differences in age- and Alzheimer's disease-related demyelination.
Science (New York, N.Y.)
Amyloid-β positivity is less prevalent in cognitively unimpaired KLOTHO KL-VS heterozygotes.
Journal of Alzheimer's disease : JAD
β-Amyloid in Cognitively Unimpaired Individuals-Blame Mom?
JAMA neurology
A second X chromosome improves cognition in aging male and female mice.
bioRxiv : the preprint server for biology
Sex and gender differences in cognitive resilience to aging and Alzheimer's disease.
Alzheimer's & dementia : the journal of the Alzheimer's Association
KLOTHO KL-VS heterozygosity is associated with diminished age-related neuroinflammation, neurodegeneration, and synaptic dysfunction in older cognitively unimpaired adults.
Alzheimer's & dementia : the journal of the Alzheimer's Association
Klotho protein concentrations as a function of sex, APOE, family history or Alzheimer’s disease biomarker status in an at-risk cohort.
Alzheimer's & Dementia
Relationships between KLOTHO and APOE4-associated ß-amyloid and tau alterations across AD continuum.
Alzheimer's & Dementia
Sex Chromosomes and Gonads Shape the Sex-Biased Transcriptomic Landscape in Tlr7-Mediated Demyelination During Aging.
bioRxiv : the preprint server for biology
Plasma phosphorylated tau-217 exhibits sex-specific prognostication of cognitive decline and brain atrophy in cognitively unimpaired adults.
Alzheimer's & dementia : the journal of the Alzheimer's Association
Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice.
Nature Aging
X chromosome factor Kdm6a enhances cognition independent of its demethylase function in the aging XY male brain.
The journals of gerontology. Series A, Biological sciences and medical sciences
The mitochondrial unfolded protein response regulates hippocampal neural stem cell aging.
Cell metabolism
Chapter 51 Sex differences in neurological and psychiatric diseases*.
Neurobiology of Brain Disorders
X CHROMOSOME-DERIVED MECHANISMS OF SEX DIFFERENCES IN LIFESPAN AND BRAIN AGING.
Innovation in Aging
AD-associated CSF biomolecular changes are attenuated in KL-VS heterozygotes.
Alzheimer's & dementia (Amsterdam, Netherlands)
KL1 domain of longevity factor klotho mimics the metabolome of cognitive stimulation and enhances cognition in young and aging mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Deep phenotyping of Alzheimer's disease leveraging electronic medical records identifies sex-specific clinical associations.
Nature communications
KIBRA, MTNR1B, and FKBP5 genotypes are associated with decreased odds of incident delirium in elderly post-surgical patients.
Scientific reports
Circulating Klotho Is Higher in Cerebrospinal Fluid than Serum and Elevated Among KLOTHO Heterozygotes in a Cohort with Risk for Alzheimer's Disease.
Journal of Alzheimer's disease : JAD
Female resilience in brain aging.
Innovation in Aging
Sex-Stratified Single-Cell RNA-Seq Analysis Identifies Sex-Specific and Cell Type-Specific Transcriptional Responses in Alzheimer's Disease Across Two Brain Regions.
Molecular neurobiology
Sex-Specific Association of the X Chromosome With Cognitive Change and Tau Pathology in Aging and Alzheimer Disease.
JAMA neurology
Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer's Disease.
Frontiers in Endocrinology
Sugar sweetened beverage consumption is positively associated with Klotho levels at two years of age in LatinX youth.
BMC nutrition
Age-Related Tau Burden and Cognitive Deficits Are Attenuated in KLOTHO KL-VS Heterozygotes.
Journal of Alzheimer's disease : JAD
Age-Related Tau Burden and Cognitive Deficits Are Attenuated in KLOTHO KL-VS Heterozygotes.
Journal of Alzheimer's disease : JAD
A second X chromosome contributes to resilience in a mouse model of Alzheimer's disease.
Science translational medicine
Longevity Gene KLOTHO and Alzheimer Disease-A Better Fate for Individuals Who Carry APOE e4.
JAMA neurology
4329 Investigating the role of Klotho in neurocognitive outcomes, brain volumes, and white matter changes in pediatric brain tumor survivors.
Journal of Clinical and Translational Science
Sexual dimorphism of physical activity on cognitive aging: Role of immune functioning.
Brain, behavior, and immunity
Best of JAMA Neurology 2019: Research That Drives Practice.
JAMA neurology
Sex difference in Alzheimer's disease: An updated, balanced and emerging perspective on differing vulnerabilities.
Handbook of clinical neurology
Pathways to brain resilience.
Nature medicine
Cognitive aging is not created equally: differentiating unique cognitive phenotypes in "normal" adults.
Neurobiology of aging
QOL-47. ApoE4 AS A GENETIC PREDICTOR FOR NEUROCOGNITIVE OUTCOMES IN PEDIATRIC BRAIN TUMOR SURVIVORS.
Neuro-Oncology
The Way of Tau: Secretion and Synaptic Dysfunction.
Trends in molecular medicine
Cord blood klotho levels are inversely associated with leptin in healthy Latino neonates at risk for obesity.
Journal of pediatric endocrinology & metabolism : JPEM
BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention.
Neurology
Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging.
Brain imaging and behavior
Sex biology contributions to vulnerability to Alzheimer's disease: A think tank convened by the Women's Alzheimer's Research Initiative.
Alzheimer's & dementia : the journal of the Alzheimer's Association
LONGEVITY GENE KLOTHO ALTERS APOE4-RELATED CORTICAL THINNING: FINDINGS FROM THE WISCONSIN REGISTRY FOR ALZHEIMER’S PREVENTION.
Alzheimer's & Dementia
LONGEVITY GENE KLOTHO ALTERS APOE4-RELATED CORTICAL THINNING: FINDINGS FROM THE WISCONSIN REGISTRY FOR ALZHEIMER’S PREVENTION.
Alzheimer's & Dementia
Network dysfunction in a-synuclein transgenic mice and human Lewy body dementia.
Annals of clinical and translational neurology
Longevity factor klotho and chronic psychological stress.
Translational psychiatry
Variation in Longevity Gene KLOTHO is Associated with Greater Cortical Volumes in Aging (S41.002).
Neurology
Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory.
Nature neuroscience
Variation in longevity gene KLOTHO is associated with greater cortical volumes.
Annals of clinical and translational neurology
Life extension factor klotho enhances cognition.
Cell reports
Reversible suppression of electrocerebral activity.
The Neurohospitalist
Sex and gonadal hormones in mouse models of Alzheimer's disease: what is relevant to the human condition?
Biology of sex differences
T-cell lymphoproliferative disorder following mycophenolate treatment for myasthenia gravis.
Muscle & nerve
Collagen VI protects neurons against Abeta toxicity.
Nature neuroscience
P1-465: Role of collagen VI in Alzheimer's disease: Potential mechanisms of protection.
Alzheimer's & Dementia
A case of paraneoplastic myelopathy associated with the neuromyelitis optica antibody.
Nature clinical practice. Neurology
Stroke injury in rats causes an increase in activin A gene expression which is unaffected by oestradiol treatment.
Journal of neuroendocrinology
Are estrogens protective or risk factors in brain injury and neurodegeneration? Reevaluation after the Women's health initiative.
Endocrine reviews
Activin gene expression increases after stroke injury: Modulation by estradiol.
Experimental and Clinical Endocrinology & Diabetes
Are Estrogens Protective or Risk Factors in the Brain? Insights Derived From Animal Models.
Endocrine Aspects of Successful Aging: Genes, Hormones and Lifestyles
Mechanisms of sex-based neuropathologies.
Principles of Sex-based Differences in Physiology
Estradiol attenuates programmed cell death after stroke-like injury.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Estradiol differentially regulates c-Fos after focal cerebral ischemia.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Ms Jones: reflections on aging, illness, and medicine.
Family medicine
Estrogen and neuroprotection: from clinical observations to molecular mechanisms.
Dialogues in clinical neuroscience
Neuroendocrine modulation and repercussions of female reproductive aging.
Recent progress in hormone research
Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies.
Brain research. Brain research reviews
In Vitro and In Vivo Approaches to the Study of the Neuroprotective Actions of Estradiol.
Neuroplasticity, Development, and Steroid Hormone Action
Minireview: Neuroprotective Effects of Estrogen—New Insights into Mechanisms of Action.
Endocrinology
Minireview: neuroprotective effects of estrogen-new insights into mechanisms of action.
Endocrinology
Estrogen receptor a, not ß, is a critical link in estradiol-mediated protection against brain injury.
Proceedings of the National Academy of Sciences
Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury.
Proceedings of the National Academy of Sciences of the United States of America
Estrogens: trophic and protective factors in the adult brain.
Frontiers in neuroendocrinology
Estradiol protects against ischemic brain injury in middle-aged rats.
Biology of reproduction
Estradiol protects against injury-induced cell death in cortical explant cultures: a role for estrogen receptors.
Brain research
Estradiol is a neuroprotective factor in in vivo and in vitro models of brain injury.
Journal of neurocytology
Neuroprotective actions of estradiol in the adult and aging brain: Potential mechanisms of action.
Neurobiology of aging
Estradiol: a protective and trophic factor in the brain.
Journal of Alzheimer's disease : JAD
Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Neuroendocrine influences and repercussions of the menopause.
Endocrine reviews
Estradiol protects against ischemic injury.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism